葛根素保护实验性脑梗死大鼠血-脑脊液屏障及作用机制的研究  

The protective role of puerarin in blood-brain barrier of rat with experiment cerebral ischemia

作　　者：刘亚强 郭家辉 杨燚[1] 祝春华[1] Liu Yaqiang;Guo Jiahui;Yang Yi;Zhu Chunhua(Department of Neurology,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院神经内科,石家庄050000

出　　处：《脑与神经疾病杂志》2020年第4期218-221,共4页Journal of Brain and Nervous Diseases

基　　金：河北省青年科学基金(H2016206373)。

摘　　要：目的探讨葛根素对脑梗死大鼠血-脑脊液屏障(BBB)的保护作用及可能机制。方法SD大鼠随机分为假手术组、对照组和葛根素组。线栓法建立右侧永久性大脑中动脉闭塞(pMCAO)模型。假手术组仅分离颈动脉,对照组和葛根素组分别于pMCAO术后立即予溶剂和葛根素(100mg·kg-1,溶于10%酒精)腹腔注射。采用伊文斯兰染色评价BBB完整性,干湿重法测定脑组织水肿,TTC染色观察脑梗死体积,改良的Longa分级法评价神经功能。并采用Western blot和qR-T PCR来观察pMCAO术后24 h基质金属蛋白酶-9(MMP-9)和claudin-5的表达变化。结果葛根素能够显著改善神经功能,减轻脑水肿,减小梗死体积,减少伊文斯兰染料的渗出BBB,并下调MMP-9表达和上调claudin-5表达。结论葛根素减轻pMCAO术后BBB损害,减轻脑水肿,减小脑梗死体积,抑制MMP-9和上调claudin-5表达可能是葛根素保护BBB的分子机制。Objective To investigate the role of puerarin in the permanent cerebral ischemia of rats and the potential mechanisms.Methods Male Sprague-Dawley rats were randomly divided into 3 groups:shamoperated group,vehicle group,puerarin group.The experiment cerebral ischemia was established using permanent middle cerebral artery occlusion(MCAO)in rats,the isolated carotid artery was separated only in sham-operated group.Vehicle and puerarin(100mg·kg-1 in 10%alcohol)were injected intraperitoneally in vehicle group and puerarin group respectively after pMCAO operation.The brain edema was measured by dry-wet weight method,the infarct volume was detected by TTC stain,BBB integrity was measured by evans blue dye leakage and neurological deficits was evaluated by modified Longa grading method.MMP-9 and claudin-5 expression were explored by western blot and qRT-PCR.Results Puerarin significantly improve neurological deficits,reduce cerebral edema,alleviated infarct volume and decreased evans blue dye leakage,down-regulated MMP-9 level and up-regulated claudin-5 expression.Conclusion Puerarin improved BBB permeability,reduce brain edema and infarct volume,and down-regulating MMP-9 and up-regulating claudin-5 levele may be the molecular mechanisms of puerarin protecting BBB after pMCAO operation.

关 键 词：脑梗死 血-脑脊液屏障 葛根素 基质金属蛋白酶-9 CLAUDIN-5 

分 类 号：R734.32[医药卫生—肿瘤]